Inhibitory effects of puerarin on myometrium contraction during rat menstrual cycle and its underlying mechanisms
Main Article Content
Abstract
Purpose: To observe uterine contractile patterns in various phases of the menstrual cycle, and elucidate mechanisms involved in the inhibition of puerarin on rat uterine contraction.
Methods: Uterus strips of Sprague Dawley rat were suspended in tissue chambers to measure the contractile activities of the strips.
Results: Isolated myometrial strips possessed three typical forms of contractions: spontaneous rhythmic contraction, tonic contraction, and irregular contraction, respectively appearing in varied phases of the rat menstrual cycle. Puerarin not only dose-dependently inhibited spontaneous contraction but also could dose-dependently inhibit KCl or PGF2α-induced uterus contractions. The inhibitory effects induced by puerarin in KCl-precontracted myometrial strips could be attenuated partly by β2 adrenoceptor antagonist ICI118551 but had no obvious changes prior to treatment with glibenclamide, Nw-L-nitro-arginine, ICI 182,780, tamoxifen or indomethacin. In high K+ Ca2+-free Kreb’s solution containing 0.01 mmol/L egtazic acid (EGTA), puerarin decreased the first phase contractions induced by oxytocin, acetylcholine, or prostaglandin F2α, but did not affect the second contractions induced by CaCl2, and also had no marked effect on the concentration-response curve of CaCl2.
Conclusion: The results demonstrate that uterus contraction patterns differ during varied menstrual cycle phases. Puerarin can inhibit isolated myometrium contractions, probably due to activation of β2-adrenoceptor, and partially via reduction of Ca2+ release from the sarcoplasmic reticulum.
Keywords:
Puerarin, myometrium contraction, menstrual cycle, adrenergic receptor, Ca2 release
Article Details
How to Cite
MA, Qin et al.
Inhibitory effects of puerarin on myometrium contraction during rat menstrual cycle and its underlying mechanisms.
Medical Research Archives, [S.l.], v. 12, n. 9, sep. 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/5802>. Date accessed: 21 nov. 2024.
doi: https://doi.org/10.18103/mra.v12i9.5802.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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21. Wahabi HA, Fayed AA, Esmaeil SA, Bahkali KH. Progestogen for treating threatened miscarriage. Cochrane Database Syst Rev. 2018;8(8):CD005943. doi: 10.1002/14651858
22. Mirdamadi M, Kothencz A, Szűcs E, Benyhe S, Szécsi M, Gáspár R. Non-genomic actions of sex hormones on pregnant uterine contractility in rats: An in vitro study at term. Life Sci. 2020;263:118584. doi: 10.1016/j.lfs.2020.118584
23. An SM, Kim SS, Kim J, Park MN, Lee JE, Cho SK, et al. Expression of reproductive hormone receptors and contraction-associated genes in porcine uterus during the estrous cycle. Mol Med Rep. 2017;15(6):4176-4184. doi: 10.3892/mmr.2017.6518
24. MacLean JA 2nd, Hayashi K. Progesterone Actions and Resistance in Gynecological Disorders. Cells. 2022;11(4):647. doi: 10.3390/cells11040647
25. Liu J, Feng R, Dai O, Ni H, Liu LS, Shu HZ, et al. Isoindolines and phthalides from the rhizomes of Ligusticum chuanxiong and their relaxant effects on the uterine smooth muscle. Phytochemistry. 2022;198:113159. doi: 10.1016/j.phytochem. 2022.113159
26. Ali A, Redfors B, Lundgren J, Alkhoury J, Oras J, Gan LM, et al. Effects of pretreatment with cardio stimulants and beta-blockers on isoprenaline-induced takotsubo-like cardiac dysfunction in rats. Int J Cardiol. 2019;15:281:99-104. doi: 10.1016/j.ijcard.2018.12.045
27. Bhatiya S, Choudhury S, Gari M, Singh P, Shukla A, Garg SK. Myometrial Calcium and Potassium Channels Play a Pivotal Role in Chromium-Induced Relaxation in Rat Uterus: an In Vitro Study. Biol Trace Elem Res. 2020;198(1):198-205. doi: 10.1007/s12011-020-02041-x
28. Passaglia P, Gonzaga NA, Tirapelli DP, Tirapelli LF, Tirapelli CR. Pharmacological characterization of the mechanisms underlying the relaxant effect of adrenomedullin in the rat carotid artery. J Pharm Pharmacol. 2014;66(12):1734-1746. doi: 10.1111/jphp.12299
29. Babes A, Fischer MJ, Filipovic M, Engel MA, Flonta ML, Reeh PW. The anti-diabetic drug glibenclamideis an agonist of the transient receptor potential Ankyrin 1 (TRPA1) ion channel. Eur J Pharmacol. 2013;04(1-3):15-22. doi: 10.1016/j.ejphar.2013.02.018
30. Negroni JA, Lascano EC, del Valle HF. Glibenclamide action on myocardial function and arrhythmia incidence in the healthy and diabetic heart. Cardiovasc Hematol Agents Med Chem. 2007;5(1):43-53. doi: 10.2174/18715250777931 5868
31. Zhang R, Zou Z, Zhou X, Shen X, Fan Z, Xie T, et al. Comparative Effects of Three Sulfonylureas (Glibenclamide, Glimepiride, and Gliclazide) on Proliferation and Migration of Vascular Smooth Muscle Cells. Cell Physiol Biochem. 2019;52(1):16-26. doi: 10.33594/000000002
32. Förstermann U, Sessa WC. Nitric oxide synthases Eur Heart J. 2012;33(7):829-837, 837a-837d. doi: 10.1093/eurheartj/ehr304
33. Picciano AL, Crane BR. Anitricoxidesynthase-like protein from Synechococcus produces NO/NO3-froml-arginineandNADPHin a tetrahydrobiopterin- and Ca2+-dependent manner. J Biol Chem. 2019;294(27):10708-10719. doi: 10.1074/jbc.RA119.008399
34. Totzeck M, Hendgen-Cotta UB, Luedike P, Berenbrink M, Klare JP, Steinhoff HJ, et al. Nitrite regulates hypoxic vasodilation via myoglobin-dependent nitric oxide generation. Circulation. 2012;126(3):325-334. doi: 10.1161/CIRCULATIONAHA.111.087155
35. Khan FA, Chenier TS, Murrant CL, Foster RA, Hewson J, Scholtz EL. Dose-dependent inhibition of uterine contractility by nitric oxide: A potential mechanism underlying persistent breeding-induced endometritis in the mare. Theriogenology. 2017;90:59-64. doi: 10.1016/j.theriogenology.2016.11.026
36. Yallampalli C, Izumi H, Byam-Smith M, Garfield RE. An L-arginine-nitric oxide-cyclic guanosine monophosphate system exists in the uterus and inhibits contractility during pregnancy. Am J Obstet Gynecol. 1994;170(1 Pt 1):175-185. doi: 10.1016/s0002-9378(94)70405-8
37. Powell SA, Smith BB, Timm KI, Menino AR. Expression of estrogen receptors alpha and beta in the corpus luteum and uterus from non-pregnant and pregnant llamas. Mol Reprod Dev. 2007;74(8):1043-1052. doi: 10.1002/mrd.20684
38. Nathan MR, Schmid P. A Review of Fulvestrantin Breast Cancer. Oncol Ther. 2017;5(1):17-29. doi: 10.1007/s40487-017-0046-2
39. Dawood MY, Khan-Dawood FS. Differential suppression of menstrual fluid prostaglandin F2a, prostaglandin E2, 6-keto prostaglandin F1a and thromboxane B2 by suprofen in women with primary dysmenorrhea. Prostaglandins Other Lipid Mediat. 2007;83(1-2):146-153. doi: 10.1016/j.prostaglandins.2006.10.009
40. Gu B, Zhu S, Ding X, Deng Y, Ma X, Gan J, et al. Effect of Low-Power Visible-Light-Activated Photodynamic Therapy (PDT) on primary dysmenorrhea: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial. Int J Womens. 2022;14:1029-1036
41. Yang W, Guo H, Niu J, Liu J, Su R, Bai Y, et al. Phloroglucinol inhibits oxytocin-induced contraction in rat gastric circular muscle and uterine smooth muscle. J Obstet Gynaecol. 2023;43(1):2130208. doi: 10.1080/01443615.2022.2130208
42. Earl RA, Grivell RM. Nifedipine for primary dysmenorrhoea. Cochrane Database Syst Rev. 2021;12(12):CD012912. doi: 10.1002/14651858
43. Sun L, Liu L, Zong S, Wang Z, Zhou J, Xu Z, et al. Traditional Chinese medicine Guizhi Fuling capsule used for therapy of dysmenorrheavia attenuating uterus contraction. J Ethnopharmacol. 2016;191:273-279. doi: 10.1016/j.jep.2016.06.042
44. Gestel IV, lJland MM, Hoogland HJ, Evers JLH. Endometrial wave-like activity in the non-pregnant uterus. Human Reproduction Update. 2003;9(2):131-138. doi: 10.1093/humupd/dmg011
45. Li G, Liu A, Lin M, Liao S, Wen Z. Chinese herbal formula siwutang for treating primary dysmenorrhea: A systematic review and meta-analysis of randomized controlled trials. Maturitas. 2020;138:26-35. doi: 10.1016/j.maturitas.2020.03.009
2. Domino M, Pawlinski B, Gajewska M, Jasinski T, Sady M, Gajewski Z. Uterine EMG activity in the non-pregnant sow during estrous cycle. BMC Vet Res. 2018;14(1):176. doi: 10.1186/s12917-018-1495-z
3. Dodds KN, Staikopoulos V, Beckett EA. Uterine Contractility in the Nonpregnant Mouse: Changes During the Estrous Cycle and Effects of Chloride Channel Blockade. Biol Reprod. 2015;92(6):141. doi: 10.1095/biolreprod.115.129809
4. Oki T, Douchi T, Maruta K, Nakamura S, Nagata Y. Changes in endometrial wave-like movements in accordance with the phases of menstrual cycle. J Obstet Gynaecol Res. 2002;28(3):176-181. doi: 10.1046/j.1341-8076.2002.00026.x
5. Yi Y, Adrjan B, Li J, Hu B, Roszak S. NMR studies of daidzein and puerarin: active anti-oxidants in traditional Chinese medicine. J Mol Model. 2019;26;25(7):202. doi: 10.1007/s00894-019-4090-8
6. Udomsin O, Krittanai S, Kitisripanya T, Tanaka H, Putalun W. A New Highly Selective and Specific Anti-puerarinpolyclonal Antibody for Determination of Puerarin Using a Mannich Reaction Hapten Conjugate. Pharmacogn Mag.2018;13(Suppl 4): S845-S851. doi: 10.4103/pm.pm_276_17
7. Zhou DD, Luo M, Shang A, Mao QQ, Li BY, Gan RY, et al. AntioxidantFoodComponents for the Prevention and Treatment of Cardiovascular Diseases: Effects, Mechanisms, and Clinical Studies. Oxid Med Cell Longev. 2021;2021:6627355. doi: 10.1155/2021/6627355
8. Zhang XL, Wang BB, Mo JS. Puerarin6″-O-xyloside possesses significant antitumor activities on colon cancer through inducing apoptosis. Oncol Lett. 2018;16(5):5557-5564. doi: 10.3892/ol.2018.9364
9. Gray SL, Lackey BR, Boone WR. Impact of kudzu and puerarinon sperm function. Reprod Toxicol. 2015;53:54-62. doi: 10.1016/j.reprotox.2015.03.01
10. Yu J, Zhao L, Zhang D, Zhai D, Shen W, Bai L, et al. The effects and possible mechanisms of puerarin to treat endometriosis model rats. Evid Based Complement Alternat Med. 2015;2015:269138. doi: 10.1155/2015/269138
11. Zhao CP, Chen GY, Wang Y, Chen H, Yu JW, Yang FQ. Evaluation of Enzyme Inhibitory Activity of flavonoids by Polydopamine-Modified Hollow Fiber-Immobilized Xanthine Oxidase. Molecules. 2021;26(13):3931. doi: 10.3390/molecules26133931
12. Guo YJ, Liang DL, Xu ZS, Ye Q. In vivo inhibitory effects of puerarin on selected ratcytochromeP450isoenzymes. Pharmazie. 2014;69(5):367-370
13. Ma J, Wang C, Sun Y, Pang L, Zhu S, Liu Y, et al. Comparative study of oral and intranasal puerarin for prevention of brain injury induced by acute high-altitude hypoxia. Int J Pharm. 2020;15:591:120002. doi: 10.1016/j.ijpharm.2020.120002
14. Zhou YX, Zhang H, Peng C. Effects of puerarin on the Prevention and Treatment of Cardiovascular Diseases. Front Pharmacol. 2021;12:771793. doi: 10.3389/fphar.2021.771793
15. Jiang Z, Cui X, Qu P, Shang C, Xiang M, Wang J. Roles and mechanisms of puerarinon cardiovascular disease: A review. Biomed Pharmacother. 2022;147:112655. doi: 10.1016/j.biopha.2022
16. Lin YH, Ni XB, Zhang JW, Ou CW, He XQ, Dai WJ, et al. Effect of puerarin on action potential and sodium channel activation in human hypertrophic cardiomyocytes. Biosci Rep. 2022;28;40(2):BSR20193369. doi: 10.1042/BSR20193369
17. Chen M, Xiang L, Wu G, Liao Y, Cai Y. Puerarin Inhibits Endothelium-Dependent Contractions in Mouse Carotid Arteries. Med Sci Monit. 2022;26:e923163. doi: 10.12659/MSM.923163
18. Domino M, Domino K, Pawlinski B, Sady M, Gajewska M, Gajewski Z. Computational multivariate modeling of electrical activity of the porcine uterus during spontaneous and hormone-induced oestrus. Exp Physiol. 2019;104(3):322-333. doi: 10.1113/EP087451
19. Modzelewska B, Jóźwik M, Jóźwik M, Tylicka M, Kleszczewski T. The effects of extended nitric oxide release on responses of the human non-pregnant myometrium to endothelin-1 or vasopressin. Pharmacol Rep. 2019;71(5):892-898. doi: 10.1016/j.pharep.2019.05.003
20. Hutchings G, Williams O, Cretoiu D, Ciontea SM. Myometrial interstitial cells and the coordination of myometrial contractility. J Cell Mol Med. 2009;13(10):4268-4282. doi: 10.1111/j.1582-4934.2009.00894.x
21. Wahabi HA, Fayed AA, Esmaeil SA, Bahkali KH. Progestogen for treating threatened miscarriage. Cochrane Database Syst Rev. 2018;8(8):CD005943. doi: 10.1002/14651858
22. Mirdamadi M, Kothencz A, Szűcs E, Benyhe S, Szécsi M, Gáspár R. Non-genomic actions of sex hormones on pregnant uterine contractility in rats: An in vitro study at term. Life Sci. 2020;263:118584. doi: 10.1016/j.lfs.2020.118584
23. An SM, Kim SS, Kim J, Park MN, Lee JE, Cho SK, et al. Expression of reproductive hormone receptors and contraction-associated genes in porcine uterus during the estrous cycle. Mol Med Rep. 2017;15(6):4176-4184. doi: 10.3892/mmr.2017.6518
24. MacLean JA 2nd, Hayashi K. Progesterone Actions and Resistance in Gynecological Disorders. Cells. 2022;11(4):647. doi: 10.3390/cells11040647
25. Liu J, Feng R, Dai O, Ni H, Liu LS, Shu HZ, et al. Isoindolines and phthalides from the rhizomes of Ligusticum chuanxiong and their relaxant effects on the uterine smooth muscle. Phytochemistry. 2022;198:113159. doi: 10.1016/j.phytochem. 2022.113159
26. Ali A, Redfors B, Lundgren J, Alkhoury J, Oras J, Gan LM, et al. Effects of pretreatment with cardio stimulants and beta-blockers on isoprenaline-induced takotsubo-like cardiac dysfunction in rats. Int J Cardiol. 2019;15:281:99-104. doi: 10.1016/j.ijcard.2018.12.045
27. Bhatiya S, Choudhury S, Gari M, Singh P, Shukla A, Garg SK. Myometrial Calcium and Potassium Channels Play a Pivotal Role in Chromium-Induced Relaxation in Rat Uterus: an In Vitro Study. Biol Trace Elem Res. 2020;198(1):198-205. doi: 10.1007/s12011-020-02041-x
28. Passaglia P, Gonzaga NA, Tirapelli DP, Tirapelli LF, Tirapelli CR. Pharmacological characterization of the mechanisms underlying the relaxant effect of adrenomedullin in the rat carotid artery. J Pharm Pharmacol. 2014;66(12):1734-1746. doi: 10.1111/jphp.12299
29. Babes A, Fischer MJ, Filipovic M, Engel MA, Flonta ML, Reeh PW. The anti-diabetic drug glibenclamideis an agonist of the transient receptor potential Ankyrin 1 (TRPA1) ion channel. Eur J Pharmacol. 2013;04(1-3):15-22. doi: 10.1016/j.ejphar.2013.02.018
30. Negroni JA, Lascano EC, del Valle HF. Glibenclamide action on myocardial function and arrhythmia incidence in the healthy and diabetic heart. Cardiovasc Hematol Agents Med Chem. 2007;5(1):43-53. doi: 10.2174/18715250777931 5868
31. Zhang R, Zou Z, Zhou X, Shen X, Fan Z, Xie T, et al. Comparative Effects of Three Sulfonylureas (Glibenclamide, Glimepiride, and Gliclazide) on Proliferation and Migration of Vascular Smooth Muscle Cells. Cell Physiol Biochem. 2019;52(1):16-26. doi: 10.33594/000000002
32. Förstermann U, Sessa WC. Nitric oxide synthases Eur Heart J. 2012;33(7):829-837, 837a-837d. doi: 10.1093/eurheartj/ehr304
33. Picciano AL, Crane BR. Anitricoxidesynthase-like protein from Synechococcus produces NO/NO3-froml-arginineandNADPHin a tetrahydrobiopterin- and Ca2+-dependent manner. J Biol Chem. 2019;294(27):10708-10719. doi: 10.1074/jbc.RA119.008399
34. Totzeck M, Hendgen-Cotta UB, Luedike P, Berenbrink M, Klare JP, Steinhoff HJ, et al. Nitrite regulates hypoxic vasodilation via myoglobin-dependent nitric oxide generation. Circulation. 2012;126(3):325-334. doi: 10.1161/CIRCULATIONAHA.111.087155
35. Khan FA, Chenier TS, Murrant CL, Foster RA, Hewson J, Scholtz EL. Dose-dependent inhibition of uterine contractility by nitric oxide: A potential mechanism underlying persistent breeding-induced endometritis in the mare. Theriogenology. 2017;90:59-64. doi: 10.1016/j.theriogenology.2016.11.026
36. Yallampalli C, Izumi H, Byam-Smith M, Garfield RE. An L-arginine-nitric oxide-cyclic guanosine monophosphate system exists in the uterus and inhibits contractility during pregnancy. Am J Obstet Gynecol. 1994;170(1 Pt 1):175-185. doi: 10.1016/s0002-9378(94)70405-8
37. Powell SA, Smith BB, Timm KI, Menino AR. Expression of estrogen receptors alpha and beta in the corpus luteum and uterus from non-pregnant and pregnant llamas. Mol Reprod Dev. 2007;74(8):1043-1052. doi: 10.1002/mrd.20684
38. Nathan MR, Schmid P. A Review of Fulvestrantin Breast Cancer. Oncol Ther. 2017;5(1):17-29. doi: 10.1007/s40487-017-0046-2
39. Dawood MY, Khan-Dawood FS. Differential suppression of menstrual fluid prostaglandin F2a, prostaglandin E2, 6-keto prostaglandin F1a and thromboxane B2 by suprofen in women with primary dysmenorrhea. Prostaglandins Other Lipid Mediat. 2007;83(1-2):146-153. doi: 10.1016/j.prostaglandins.2006.10.009
40. Gu B, Zhu S, Ding X, Deng Y, Ma X, Gan J, et al. Effect of Low-Power Visible-Light-Activated Photodynamic Therapy (PDT) on primary dysmenorrhea: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial. Int J Womens. 2022;14:1029-1036
41. Yang W, Guo H, Niu J, Liu J, Su R, Bai Y, et al. Phloroglucinol inhibits oxytocin-induced contraction in rat gastric circular muscle and uterine smooth muscle. J Obstet Gynaecol. 2023;43(1):2130208. doi: 10.1080/01443615.2022.2130208
42. Earl RA, Grivell RM. Nifedipine for primary dysmenorrhoea. Cochrane Database Syst Rev. 2021;12(12):CD012912. doi: 10.1002/14651858
43. Sun L, Liu L, Zong S, Wang Z, Zhou J, Xu Z, et al. Traditional Chinese medicine Guizhi Fuling capsule used for therapy of dysmenorrheavia attenuating uterus contraction. J Ethnopharmacol. 2016;191:273-279. doi: 10.1016/j.jep.2016.06.042
44. Gestel IV, lJland MM, Hoogland HJ, Evers JLH. Endometrial wave-like activity in the non-pregnant uterus. Human Reproduction Update. 2003;9(2):131-138. doi: 10.1093/humupd/dmg011
45. Li G, Liu A, Lin M, Liao S, Wen Z. Chinese herbal formula siwutang for treating primary dysmenorrhea: A systematic review and meta-analysis of randomized controlled trials. Maturitas. 2020;138:26-35. doi: 10.1016/j.maturitas.2020.03.009